The Experts below are selected from a list of 1998 Experts worldwide ranked by ideXlab platform
Mary Jeanne Kreek - One of the best experts on this subject based on the ideXlab platform.
-
effects of the plant derived hallucinogen salvinorin a on basal dopamine levels in the caudate putamen and in a conditioned place aversion assay in mice agonist actions at Kappa opioid receptors
Psychopharmacology, 2005Co-Authors: Yong Zhang, Eduardo R Butelman, Stefan D Schlussman, Mary Jeanne KreekAbstract:Salvinorin A is a naturally occurring hallucinogen derived from the plant Salvia divinorum. Salvinorin A is also a potent and selective Kappa opioid receptor agonist in vitro. It has been shown that Kappa Agonists decrease dopamine levels in the caudate putamen and nucleus accumbens and cause conditioned place aversion in rodents. To study the effects of salvinorin A on basal dopamine levels in the caudate putamen and nucleus accumbens, and to determine whether salvinorin A induces conditioned place preference or aversion and changes in locomotor activity in the mouse. In the first experiment, changes in dopamine levels in these brain regions after administration of salvinorin A were measured with in vivo microdialysis. In the second experiment, we examined whether salvinorin A led to conditioned place preference or aversion, and changes in locomotor activity during conditioning sessions. The higher doses of salvinorin A studied (1.0 mg/kg and 3.2 mg/kg, i.p.) significantly decreased dopamine levels in the caudate putamen, but not in the nucleus accumbens, and this effect was completely blocked by pre-injection with 10 mg/kg of the Kappa opioid receptor antagonist nor-binaltorphimine. The same doses of salvinorin A caused conditioned place aversion and decreased locomotor activity. The inhibitory effect of salvinorin A on striatal dopamine levels may contribute to its induction of conditioned place aversion and decreases in locomotion in mice. These findings are consistent with the in vitro characterization of salvinorin A as a Kappa opioid receptor agonist. It is of interest that a compound such as salvinorin A, that lowers striatal dopamine levels and leads to conditioned place aversion in rodents, is self-administered by humans under certain conditions.
-
effects of the plant derived hallucinogen salvinorin a on basal dopamine levels in the caudate putamen and in a conditioned place aversion assay in mice agonist actions at Kappa opioid receptors
Psychopharmacology, 2005Co-Authors: Yong Zhang, Eduardo R Butelman, Stefan D Schlussman, Ann Ho, Mary Jeanne KreekAbstract:Rationale Salvinorin A is a naturally occurring hallucinogen derived from the plant Salvia divinorum. Salvinorin A is also a potent and selective Kappa opioid receptor agonist in vitro. It has been shown that Kappa Agonists decrease dopamine levels in the caudate putamen and nucleus accumbens and cause conditioned place aversion in rodents.
James H Woods - One of the best experts on this subject based on the ideXlab platform.
-
Kappa Opioids in Rhesus Monkeys. II. Analysis of the Antagonistic Actions of Quadazocine and fl-Funaltrexam ine’
2016Co-Authors: Unda A. Dykstra, Debra E. Gmerek, Gail Winger, James H WoodsAbstract:In rhesus monkeys, Kappa oploid Agonists have been shown to 1) increase urinary output, 2) increase tail-withdrawal latencies from warm water and 3) produce distinct discriminative stimulus effects. In order to explore further the relation between these effects and activity at the Kappa opioid receptor type, the antag-onist activity of quadazocine against several Kappa oploid ago-fists was examined with the tail-withdrawal and dwg-discrimi-nation procedures. Quadazocine dose dependently antagonized the icreases in tI-withdrawal latency produced by the Kappa Agonists bremazoane, ethylketazocine and U-50,488, as well as the discriminative stimulus effects of these drugs. The dose-ratio analysis of Schild revealed apparent pA2 values for quadazocine in combination with bremazocine, ethylketazocine and U-50,488 of 6.1, 6.4 and 6.4, respectively, with the tail-withdrawal proce
-
Kappa opioid receptor mediated effects of the plant derived hallucinogen salvinorin a on inverted screen performance in the mouse
Behavioural Pharmacology, 2005Co-Authors: William E Fantegrossi, Kelly M Kugle, Leander J Valdes, Masato Koreeda, James H WoodsAbstract:Salvinorin A is a pharmacologically active diterpene that occurs naturally in the Mexican mint Ska Maria Pastora (Salvia divinorum) and represents the first naturally occurring Kappa-opioid receptor agonist. The chemical structure of salvinorin A is novel among the opioids, and thus defines a new structural class of Kappa-opioid-receptor selective drugs. Few studies have examined the effects of salvinorin A in vivo, and fewer still have attempted to assess the agonist actions of this compound at mu-opioid, delta-opioid, and Kappa-opioid receptors using selective antAgonists. In the mouse, salvinorin A disrupted climbing behavior on an inverted screen task, indicating a rapid, but short-lived induction of sedation/motor incoordination. Similar effects were observed with the mu-agonist remifentanil and the synthetic Kappa-agonist U69,593. When behaviorally equivalent doses of all three opioids were challenged with antAgonists at doses selective for mu-opioid, delta-opioid, or Kappa-opioid receptors, results suggested that the motoric effects of remifentanil were mediated by mu-receptors, whereas those of salvinorin A and U69,593 were mediated via Kappa-receptors. Despite similar potencies and degrees of effectiveness, salvinorin A and U69,593 differed with regard to their susceptibility to antagonism by the Kappa-antagonist nor-binaltorphamine. This later finding, coupled with the novel chemical structure of the compound, is consistent with recent findings that the diterpene salvinorin A may bind to the Kappa-receptor in a manner that is qualitatively different from that of more traditional Kappa-Agonists such as the benzeneacetamide U69,593. Such pharmacological differences among these Kappa-opioids raise the possibility that the development of other diterpene-based opioids may yield important therapeutic compounds.
-
Kappa opioid receptor binding populations in rhesus monkey brain relationship to an assay of thermal antinociception
Journal of Pharmacology and Experimental Therapeutics, 1998Co-Authors: Eduardo R Butelman, Katarzyna Sobczykkojiro, Henry I Mosberg, B Van Bemmel, Gerald Zernig, James H WoodsAbstract:The binding characteristics of the Kappa opioid ligands [3H]U69,593 and [3H]bremazocine, the mu opioid ligand [3H][D-ala2,N-Me-Phe4,glycol5]enkephalin and the delta opioid ligand [3H]p-Cl-[D-pen2,5]enkephalin were studied in rhesus monkey brain membranes in saturation binding experiments and were followed by competition binding experiments with a variety of peptidic and nonpeptidic opioid ligands. The [3H]U69,593 sites appeared to be a subset of Kappa opioid receptors (Kappa-1 receptors: Kd, 1.2 nM; Bmax, 66 fmol/mg). [3H]Bremazocine (in the presence of mu and delta receptor-masking agents), bound to a larger population of Kappa receptors (Kappa-all: Kd, 0.39 nM; Bmax, 227 fmol/mg), which presumably included the aforementioned Kappa-1 sites. Competition binding experiments revealed that the presently defined Kappa-1 sites were similar to previously reported sites in other mammalian species, particularly in terms of the higher Kappa-1 selectivity observed with arylacetamide (e.g., U50,488) vs. benzomorphan Kappa Agonists (e.g., ethylketocyclazocine). The Kappa-selective antagonist norbinaltorphimine (nor-BNI) displayed a very small (2.3-fold) selectivity for Kappa-1 vs. Kappa-all sites. This led to the prediction that in rhesus monkeys (n = 3), systemically administered nor-BNI (10 mg/kg s.c.) should have a very moderate degree of antagonist selectivity for the antinociceptive effects of a putative Kappa-1-agonist, the arylacetamide U50,488 (0.1-3.2 mg/kg s.c.), vs. those of the benzomorphan Kappa agonist ethylketocyclazocine (0.01-056 mg/kg s.c.). This prediction was confirmed in vivo because nor-BNI (10 mg/kg) caused a robust and long lasting (up to 21 days) antagonism of the antinociceptive effects of U50,488 and a small but significant antagonism of ethylketocyclazocine. The arylacetamide congener Cl-977 (enadoline), which displayed an 11-fold Kappa-1 vs. Kappa-all binding selectivity, was not sensitive to nor-BNI pretreatment. This indicates that the Kappa subtype-binding profile of an agonist is not necessarily predictive of its sensitivity to nor-BNI in vivo. Overall, the present results suggest that at least two functional Kappa receptor populations may be present in rhesus monkey brain.
Eduardo R Butelman - One of the best experts on this subject based on the ideXlab platform.
-
effects of the plant derived hallucinogen salvinorin a on basal dopamine levels in the caudate putamen and in a conditioned place aversion assay in mice agonist actions at Kappa opioid receptors
Psychopharmacology, 2005Co-Authors: Yong Zhang, Eduardo R Butelman, Stefan D Schlussman, Mary Jeanne KreekAbstract:Salvinorin A is a naturally occurring hallucinogen derived from the plant Salvia divinorum. Salvinorin A is also a potent and selective Kappa opioid receptor agonist in vitro. It has been shown that Kappa Agonists decrease dopamine levels in the caudate putamen and nucleus accumbens and cause conditioned place aversion in rodents. To study the effects of salvinorin A on basal dopamine levels in the caudate putamen and nucleus accumbens, and to determine whether salvinorin A induces conditioned place preference or aversion and changes in locomotor activity in the mouse. In the first experiment, changes in dopamine levels in these brain regions after administration of salvinorin A were measured with in vivo microdialysis. In the second experiment, we examined whether salvinorin A led to conditioned place preference or aversion, and changes in locomotor activity during conditioning sessions. The higher doses of salvinorin A studied (1.0 mg/kg and 3.2 mg/kg, i.p.) significantly decreased dopamine levels in the caudate putamen, but not in the nucleus accumbens, and this effect was completely blocked by pre-injection with 10 mg/kg of the Kappa opioid receptor antagonist nor-binaltorphimine. The same doses of salvinorin A caused conditioned place aversion and decreased locomotor activity. The inhibitory effect of salvinorin A on striatal dopamine levels may contribute to its induction of conditioned place aversion and decreases in locomotion in mice. These findings are consistent with the in vitro characterization of salvinorin A as a Kappa opioid receptor agonist. It is of interest that a compound such as salvinorin A, that lowers striatal dopamine levels and leads to conditioned place aversion in rodents, is self-administered by humans under certain conditions.
-
effects of the plant derived hallucinogen salvinorin a on basal dopamine levels in the caudate putamen and in a conditioned place aversion assay in mice agonist actions at Kappa opioid receptors
Psychopharmacology, 2005Co-Authors: Yong Zhang, Eduardo R Butelman, Stefan D Schlussman, Ann Ho, Mary Jeanne KreekAbstract:Rationale Salvinorin A is a naturally occurring hallucinogen derived from the plant Salvia divinorum. Salvinorin A is also a potent and selective Kappa opioid receptor agonist in vitro. It has been shown that Kappa Agonists decrease dopamine levels in the caudate putamen and nucleus accumbens and cause conditioned place aversion in rodents.
-
Kappa opioid receptor binding populations in rhesus monkey brain relationship to an assay of thermal antinociception
Journal of Pharmacology and Experimental Therapeutics, 1998Co-Authors: Eduardo R Butelman, Katarzyna Sobczykkojiro, Henry I Mosberg, B Van Bemmel, Gerald Zernig, James H WoodsAbstract:The binding characteristics of the Kappa opioid ligands [3H]U69,593 and [3H]bremazocine, the mu opioid ligand [3H][D-ala2,N-Me-Phe4,glycol5]enkephalin and the delta opioid ligand [3H]p-Cl-[D-pen2,5]enkephalin were studied in rhesus monkey brain membranes in saturation binding experiments and were followed by competition binding experiments with a variety of peptidic and nonpeptidic opioid ligands. The [3H]U69,593 sites appeared to be a subset of Kappa opioid receptors (Kappa-1 receptors: Kd, 1.2 nM; Bmax, 66 fmol/mg). [3H]Bremazocine (in the presence of mu and delta receptor-masking agents), bound to a larger population of Kappa receptors (Kappa-all: Kd, 0.39 nM; Bmax, 227 fmol/mg), which presumably included the aforementioned Kappa-1 sites. Competition binding experiments revealed that the presently defined Kappa-1 sites were similar to previously reported sites in other mammalian species, particularly in terms of the higher Kappa-1 selectivity observed with arylacetamide (e.g., U50,488) vs. benzomorphan Kappa Agonists (e.g., ethylketocyclazocine). The Kappa-selective antagonist norbinaltorphimine (nor-BNI) displayed a very small (2.3-fold) selectivity for Kappa-1 vs. Kappa-all sites. This led to the prediction that in rhesus monkeys (n = 3), systemically administered nor-BNI (10 mg/kg s.c.) should have a very moderate degree of antagonist selectivity for the antinociceptive effects of a putative Kappa-1-agonist, the arylacetamide U50,488 (0.1-3.2 mg/kg s.c.), vs. those of the benzomorphan Kappa agonist ethylketocyclazocine (0.01-056 mg/kg s.c.). This prediction was confirmed in vivo because nor-BNI (10 mg/kg) caused a robust and long lasting (up to 21 days) antagonism of the antinociceptive effects of U50,488 and a small but significant antagonism of ethylketocyclazocine. The arylacetamide congener Cl-977 (enadoline), which displayed an 11-fold Kappa-1 vs. Kappa-all binding selectivity, was not sensitive to nor-BNI pretreatment. This indicates that the Kappa subtype-binding profile of an agonist is not necessarily predictive of its sensitivity to nor-BNI in vivo. Overall, the present results suggest that at least two functional Kappa receptor populations may be present in rhesus monkey brain.
Yong Zhang - One of the best experts on this subject based on the ideXlab platform.
-
effects of the plant derived hallucinogen salvinorin a on basal dopamine levels in the caudate putamen and in a conditioned place aversion assay in mice agonist actions at Kappa opioid receptors
Psychopharmacology, 2005Co-Authors: Yong Zhang, Eduardo R Butelman, Stefan D Schlussman, Mary Jeanne KreekAbstract:Salvinorin A is a naturally occurring hallucinogen derived from the plant Salvia divinorum. Salvinorin A is also a potent and selective Kappa opioid receptor agonist in vitro. It has been shown that Kappa Agonists decrease dopamine levels in the caudate putamen and nucleus accumbens and cause conditioned place aversion in rodents. To study the effects of salvinorin A on basal dopamine levels in the caudate putamen and nucleus accumbens, and to determine whether salvinorin A induces conditioned place preference or aversion and changes in locomotor activity in the mouse. In the first experiment, changes in dopamine levels in these brain regions after administration of salvinorin A were measured with in vivo microdialysis. In the second experiment, we examined whether salvinorin A led to conditioned place preference or aversion, and changes in locomotor activity during conditioning sessions. The higher doses of salvinorin A studied (1.0 mg/kg and 3.2 mg/kg, i.p.) significantly decreased dopamine levels in the caudate putamen, but not in the nucleus accumbens, and this effect was completely blocked by pre-injection with 10 mg/kg of the Kappa opioid receptor antagonist nor-binaltorphimine. The same doses of salvinorin A caused conditioned place aversion and decreased locomotor activity. The inhibitory effect of salvinorin A on striatal dopamine levels may contribute to its induction of conditioned place aversion and decreases in locomotion in mice. These findings are consistent with the in vitro characterization of salvinorin A as a Kappa opioid receptor agonist. It is of interest that a compound such as salvinorin A, that lowers striatal dopamine levels and leads to conditioned place aversion in rodents, is self-administered by humans under certain conditions.
-
effects of the plant derived hallucinogen salvinorin a on basal dopamine levels in the caudate putamen and in a conditioned place aversion assay in mice agonist actions at Kappa opioid receptors
Psychopharmacology, 2005Co-Authors: Yong Zhang, Eduardo R Butelman, Stefan D Schlussman, Ann Ho, Mary Jeanne KreekAbstract:Rationale Salvinorin A is a naturally occurring hallucinogen derived from the plant Salvia divinorum. Salvinorin A is also a potent and selective Kappa opioid receptor agonist in vitro. It has been shown that Kappa Agonists decrease dopamine levels in the caudate putamen and nucleus accumbens and cause conditioned place aversion in rodents.
Jussara Do M Carmo - One of the best experts on this subject based on the ideXlab platform.
-
effects of nalfurafine on the reinforcing thermal antinociceptive and respiratory depressant effects of oxycodone modeling an abuse deterrent opioid analgesic in rats
Psychopharmacology, 2017Co-Authors: Andrew E Townsend, Jennifer E Naylor, Stevens S Negus, Shelley R Edwards, Hina N Qureshi, Hunter W Mclendon, Christopher R Mccurdy, Coco N Kapanda, Jussara Do M CarmoAbstract:Rationale Strategies to reduce the misuse of mu opioid Agonists are critically needed. Previous work has shown that Kappa opioid Agonists can diminish the abuse-related effects and augment the antinociceptive effects of mu Agonists. However, use of traditional Kappa Agonists is limited by their dysphoric side effects.
-
effects of nalfurafine on the reinforcing thermal antinociceptive and respiratory depressant effects of oxycodone modeling an abuse deterrent opioid analgesic in rats
Psychopharmacology, 2017Co-Authors: Andrew E Townsend, Jennifer E Naylor, Stevens S Negus, Shelley R Edwards, Hina N Qureshi, Hunter W Mclendon, Christopher R Mccurdy, Coco N Kapanda, Jussara Do M CarmoAbstract:Strategies to reduce the misuse of mu opioid Agonists are critically needed. Previous work has shown that Kappa opioid Agonists can diminish the abuse-related effects and augment the antinociceptive effects of mu Agonists. However, use of traditional Kappa Agonists is limited by their dysphoric side effects. The current study examined the effects of nalfurafine, a clinically available atypical Kappa agonist, on the reinforcing, thermal antinociceptive, and respiratory-depressant effects of oxycodone in male rats. To determine oxycodone/nalfurafine mixture proportions to be examined intravenously across procedures, a progressive ratio (PR) self-administration procedure compared the reinforcing effects of oxycodone (56 μg/kg/inj) available alone or as a mixture with co-administered nalfurafine (0.32, 1, or 3.2 μg/kg/inj), corresponding to oxycodone/nalfurafine proportions of 175:1, 56:1, and 18:1, respectively. Next, PR and thermal antinociception dose-effect functions were each determined for oxycodone, nalfurafine, and the same oxycodone/nalfurafine mixture proportions. Finally, the respiratory-depressant effects of equi-antinociceptive doses of oxycodone, nalfurafine, and the mixtures were compared. Nalfurafine decreased the reinforcing effects of oxycodone, and the 18:1 mixture did not function as a reinforcer. Oxycodone and nalfurafine each produced dose-dependent antinociception, and the mixtures produced additive antinociception. In addition, antinociceptive doses of the 56:1 and 18:1 mixtures did not produce respiratory depression. These results suggest that nalfurafine may augment the thermal antinociceptive effects while reducing the reinforcing and respiratory-depressant effects of oxycodone.
